Lovastatin blocks N-ras oncogene-induced neuronal differentiation.
ras p21 must be posttranslationally processed in order to be localized to the inner plasma membrane. The first obligatory processing step is the farnesylation of ras p21. Lovastatin, a competitive inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, may prevent the farnesylation of de novo synthesized ras p21. We demonstrate that N-ras oncogene-induced neuronal differentiation of UR61J rat pheochromocytoma cells is blocked by lovastatin. Our data show that this effect is due to the inhibition of ras p21 farnesylation. The results suggest that ras oncogene-induced phenotype in mammalian cells may be eliminated by preventing the proper processing of ras p21.
Mendola
C E
CE
Molecular Biology Section, Lederle Laboratories, American Cyanamid Company, Pearl River, New York 10965.
Backer
J M
JM
D000818:Animals; D015152:Blotting, Northern; D002454:Cell Differentiation / Q000187:drug effects; D011905:Genes, ras / Q000187:drug effects*; D008148:Lovastatin / Q000494:pharmacology*; D009474:Neurons / Q000187:drug effects*; D015689:Oncogene Protein p21(ras) / Q000187:drug effects; D011233:Precipitin Tests; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D013462:Sulfur Radioisotopes; D014407:Tumor Cells, Cultured
D013462:Sulfur Radioisotopes; D008148:Lovastatin; D015689:Oncogene Protein p21(ras)